Synthetic peptides based on the octapeptide sequence His-Pro-Phe-His-Leu-Leu-Val-Tyr, found between positions six and thirteen of natural substrate, act as competitive inhibitors for the enzyme renin. The inhibitors are made by solid phase peptide synthesis (SPPS). Effectiveness of the peptides is controlled by both the solubility and inhibitory constant. Addition of prolyl-resides to the N-terminus of the basic Octapeptide and its analogs increases solubility at physiologic pH between two and ten fold. Studies with labeled peptides show that the solubility of both octapeptide and Pro-octapeptide is at a minimum at pH 6.5. On either side of this minimum solubility of the Pro-octapeptide increases rapidly while that of the octapeptide remains low and relatively constant. Inhibitory constant (Ki) of the peptides is dependent on the lipophilicity of residues on either side of the cleavage site. The equation pKi equals 0.72pi plus 7.14 (r equals 0.999) describes activity of inhibitors having an aromatic residue in the cleavage site. Ki of Pro-(Phe(4Cl)6) octapeptide was predicted to be 1.3 micrometer. Synthesis of this compound yielded a renin inhibitor with Ki of 1.2 micrometer. BIBLIOGRAPHIC REFERENCES: Burton, J., Poulsen, K., and Haber, E.: The use of homopolymers in the design of peptide inhibitors of renin. Advances in Chemistry, 1977, in press. Poulsen, K., Burton, J., and Haber, E.: The specificity of renin. Biochim. Biophys. Acta, 1977, in press.